Mechanistic insights for the transprotection of tertiary amines with Boc(2)O via charged carbamates: access to both enantiomers of 2-azanorbornane-3-exo-carboxylic acids

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Sampaio Dias, IE (Author) Other; Silva Reis, SC (Author) Other; da Silva, LP (Author) FCUP; Garcia Mera, X (Author) Other; Maestro, MA (Author) Other; Rodriguez Borges, JE (Author) FCUP

Journal

Title: Organic Chemistry Frontiers

Vol. 6

Pages: 3540-3554

ISSN: 2052-4110

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00R-5MN

DOI: 10.1039/c9qo00957d

Abstract (EN): Herein we present a new synthesis methodology for the transprotection of the 1-phenylethyl protected tertiary amines to tert-butyloxycarbonyl (Boc) derivatives under exocyclic N-C hydrogenolysis catalyzed by Pd/C. We provide mechanistic insights into the N-dealkylation of hindered tertiary amines under the unrecognized role of tert-butyloxycarbonyl anhydride (Boc(2)O) as an additive to effectively promote the exocyclic N-C hydrogenolysis of tertiary amines by disclosing the role of Boc(2)O, which was not fully understood and studied until now. NMR and in silico experiments suggest the formation of a transient charged carbamate as the plausible intermediate. This selective transprotection enabled the development of a robust stereoselective methodology for the preparation of both enantiomers of 2-azanorbornane-3-exo-carboxylates by highly asymmetric aza-Diels-Alder reactions using (-)-8-phenylmenthol (8PM) and (+)-8-phenylneomenthol (8PnM) as chiral auxiliaries.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15